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Publication numberUS4012374 A
Publication typeGrant
Application numberUS 05/617,473
Publication dateMar 15, 1977
Filing dateSep 29, 1975
Priority dateSep 29, 1975
Publication number05617473, 617473, US 4012374 A, US 4012374A, US-A-4012374, US4012374 A, US4012374A
InventorsPeter C. Wade, B. Richard Vogt
Original AssigneeE. R. Squibb & Sons, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
1-[[4-Phenyl-piperidinyl (or tetrahydropyridinyl)]alkyl]-2,6-piperidinedione and analogs
US 4012374 A
Compounds having the formula ##STR1## wherein A is a straight or branched chain alkylene group; R1 is hydrogen, halogen, alkyl, alkoxy, alkylthio, trifluoromethyl, nitro, amino, or cyano; and n is 0, 1, or 2; are useful central nervous system depressants.
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What is claimed is:
1. A compound having the formula ##STR9##or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2; A is an alkylene group having 1 to 8 carbon atoms; and R1 is hydrogen, halogen, alkyl, alkoxy, alkylthio, trifluoromethyl, nitro, amino or cyano; wherein the alkyl, alkoxy, and alkylthio groups have 1 to 4 carbon atoms.
2. A compound in accordance with claim 1 wherein A is an alkylene group having 2 to 8 carbon atoms.
3. A compound in accordance with claim 2 wherein A is an alkylene group having 2, 3, or 4 carbon atoms.
4. A compound in accordance with claim 1 wherein A is methylene.
5. A compound in accordance with claim 1 wherein R1 is hydrogen.
6. A compound in accordance with claim 1 having the formula ##STR10##

Useful central nervous system depressant activity is exhibited by compounds having formula ##STR2## In formula I, and throughout the specification, the symbols are as defined below.

R1 can be hydrogen, halogen, alkyl, alkoxy, alkylthio, trifluoromethyl, nitro, amino, or cyano;

A can be a straight or branched chain alkylene group having 1 to 8 carbon atoms; and

N CAN BE 0, 1, OR 2.

The broken line in the piperidine nucleus represents the optional presence of ethylenic unsaturation.

The term "alkyl", as used throughout the specification, refers to alkyl groups having 1 to 4 carbon atoms.

The term "alkoxy", as used throughout the specification, refers to groups having the formula Y-O- wherein Y is alkyl as defined above.

The term "alkylthio", as used throughout the specification, refers to groups having the formula Y-S- wherein Y is alkyl as defined above.

The term "halogen", as used throughout the specification, refers to fluorine, chlorine, bromine, and iodine; fluroine, chlorine, and bromine are the preferred halogens.


The compounds of formula I, and their pharmaceutically acceptable acid addition salts, are useful in mammalian species such as rats, dogs, monkeys, and others, as central nervous system depressants, and can be used as tranquilizers for the relief of anxiety and tension states in the same manner as chlordiazepoxide. For this purpose, the compounds of this invention can be administered parenterally in single or divided doses of about 0.1 to 100 milligrams per kilogram of body weight per day, preferably about 0.5 to 15 milligrams per kilogram of body weight, two to four daily.

The components of formula I, and their pharmaceutically acceptable acid addition salts, are also useful for the treatment of inflammation in mammalian species, e.g., rats, dogs, cats, monkeys, etc. Joint tenderness and stiffness (in conditions such as rheumatoid arthritis) can be relieved by the above-described compounds. The compounds of this invention are formulated for use as anti-inflammatory agents according to accepted pharmaceutical practice in oral dosage forms such as tablets, capsules, elixirs or powders, or in an injectable form in a sterile aqueous vehicle prepared according to conventional pharmaceutical practice. The compounds of this invention can be administered in amounts of 100 milligrams per kilogram of animal body weight per day to 2 grams per kilogram of animal body weight per day, preferably 100 milligrams per kilogram of animal body weight per day to 1 gram per kilogram of animal body weight per day.

The products of formula I, wherein A is an alkylene group having 2 to 8 carbon atoms, can be prepared using as starting materials compounds having the formulas ##STR3## and

X' -- A' -- X.                                             IV

in formula IV, and throughout the specification, the symbol A' can be a straight or branched chain alkylene group having 2 to 8 carbon atoms and the symbols X and X' can be the same or different and can be halogen (preferably chlorine or bromine), alkylsulfonate (e.g., methanesulfonate or arylsulfonate (e.g., toluenesulfonate).

Reaction of a compound of formula II with a compound of formula IV yields an intermediate having the formula ##STR4## The reaction can be run in a polar organic solvent, e.g., dimethylsulfoxide or dimethhylformamide, in the presence of alkali.

Reaction of an intermediate of formula V with a pyridine derivative of formula III yields the compounds of formula I wherein A is an alkylene group having 2 to 8 carbon atoms. The reaction can be run in an organic solvent, e.g., benzene, toluene, etc., preferably in the presence of an organic or inorganic base, e.g., a tertiary amine such as ethyldiisopropylamine or an alkali metal carbonate such as sodium carbonate. While reaction conditions are not critical, the reaction will most conveniently be run at the reflux temperature of the solvent.

Alternatively, the products of formula I, wherein A is an alkylene group having 2 to 8 carbon atoms, can be prepared by first reacting a compound of formula II with an appropriate base, e.g., potassium hydroxide or thallous ethoxide. The resultant salt is reacted with a compound having the formula ##STR5## to yield the products of formula I wherein A is other than methylene.

In still another method for preparing the compounds of formula I wherein A is other than methylene, a compound having the formula ##STR6## is first reacted with a compound having the formula VIII ##STR7## to yield a compound having the formula ##STR8## Ring closure of a compound of formula IX using a dehydrating agent such as thionyl chloride, acetic anhydride or phosphorous oxychloride and/or heat yields the products of formula I wherein A is other than methylene.

The products of formula I wherein a is methylene are prepared using the Mannich reaction. A compound of formula II is reacted with a piperidine derivative of formula III, or its hydrohalogen salt, in the presence of formaldehyde or paraformaldehyde to yield the desired product. The reaction is run in a polar organic solvent such as dimethylformamide.

Additional procedures for preparing the compounds of this invention will readily apparent to a person skilled in the art. For example, compounds of formula I wherein R1 is amino, cyano, or halogen can be prepared from the corresponding nitro compounds using well known reactions. The nitro group can be reduced to an amino group using stannous chloride and a mineral acid such as hydrochloric acid, and the amino group can be converted to a halogen or cyano group using the Sandmeyer reaction.

The compounds of formula I can be converted into their pharmaceutically acceptable acid addition salts using procedures well known in the art. Exemplary of the salts contemplated are the hydrohalides, especially the hydrochloride and hydrobromide which are preferred. Other inorganic salts contemplated are the nitrate, phosphate, sulfate and the like. Organic salts are also contemplated; illustrative are the tartrate, maleate, fumarate, citrate, succinate, methanesulfonate, benzenesulfonate, toluenesulfonate, and the like.

The following examples are specific embodiments of this invention.

EXAMPLE 1 1-[4-[3,6-Dihydro-4-phenyl-1(2H)pyridinyl]butyl]-2,6-piperidinedione, hydrochloride (1:1)

A. N-(4-Bromobutyl)glutarimide

Sodium (5g) is dissolved in 100 ml of absolute ethanol and the resulting sodium ethoxide solution is added to a solution of 23g of glutarimide in 160 ml of warm absolute ethanol. A precipitate forms almost immediately, and after allowing the mixture to cool to 25 C while stirring, the solvent is removed under vacuum. To the residue is added 70 ml of dimethylformamide and 60 ml of 1,4-dibromobutane and the mixture is refluxed for 10 minutes. The solvent is removed under vacuum and the residue is shaken with hexane to remove excess 1,4-dibromobutane. The hexane layer is decanted, the residue taken up in ether, and the insoluble material filtered off. The ethereal filtrate is washed with 10% sodium hydroxide, 10% hydrochloric acid, and water, and dried over sodium sulfate. The solvent is removed under vacuum to yield 26g of N-(4-bromobutyl)glutarimide as an oil.

B. 1-[4-[3,6-Dihydro-4-phenyl-1(2H)pyridinyl]butyl]-2,6-piperidinedione, hydrochloride (1:1)

4-Phenyl-1,2,3,6-tetrahydropyridine, hydrochloride (10g) is converted to its free base and mixed with 11.0g of N-(4-bromobutyl)glutarimide and 18g of sodium carbonate in 200 ml of toluene. The mixture is refluxed for 5 hours, cooled to 25 C, and 50 ml of water is added. After stirring for 15 minutes, the layers are separated and the organic layer is filtered through fritted glass and extracted with 10% hydrochloric acid. The acid layer is made alkaline (pH 10) with sodium hydroxide producing an insoluble gum that crystallizes on standing. The supernatant is decanted and the residue is recrystallized by dissolving in methanol and slowly diluting with an equal volume of water. An oil is produced that crystallizes on standing.

The crystals are filtered off and taken up in hot ether/ethanol (10:1). The solution is treated with a 10% excess of ethereal hydrogen chloride precipitating the salt as a gum. After 30 minutes the ether is decanted and the gum taken up in a small amount of ethanol. Slow addition of a large amount of ether gives the salt as a fine granular precipitate.

The salt is filtered off and dried at 50 C (0.1 mm of Hg) for 4 hours to yield 10.4g of the title compound, melting point 159.5 C-161 C.


Following the procedure of Example 1, but substituting the compound listed in column I for glutarimide, the compound listed in column II for 1,4-dibromobutane, and the compound listed in column III for 4-phenyl-1,2,3,6-tetrahydropyridine, hydrochloride, the compound listed in column IV is obtained.

__________________________________________________________________________ExampleColumn I       Column II  Column III      Column IV__________________________________________________________________________ 2   glutarimide       1,2-dibromoethane                  4-(4-chlorophenyl)-1,2,3,6-                                  1-[2-[3,6-dihydro-4-(4-chloro-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]ethyl]-                                  2,6-piperidinedione,                                  hydrochloride 3   glutarimide       1,3-dibromopropane                  4-(4-bromophenyl)-1,2,3,6-                                  1-[3-[3,6-dihydro-4-(4-bromophenyl)                                  -                  tetrahydropyridine                                  1(2H)pyridinyl]propyl]-2,6-piper-                                  idinedione, hydrochloride 4   glutarimide       1,5-dibromopentane                  4-(2-methylphenyl)-1,2,3,6-                                  1-[5-[3,6-dihydro-4-(2-methyl-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]pentyl]-                                  2,6-piperidinedione,                                  hydrochloride 5   glutarimide       1,6-dibromohexane                  4-(3-methoxyphenyl)-1,2,3,6-                                  1-[6-[3,6-dihydro-4-(3-methoxy-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]hexyl]-                                  2,6-piperidinedione,                                  hydrochloride 6   glutarimide       1,7-dibromoheptane                  4-(4-methylthiophenyl)-1,2-                                  1-[7-[3,6-dihydro-4-(4-methyl-                  3,6-tetrahydropyridine                                  thiophenyl)-1(2H)pyridinyl]heptyl]-                                  5                                  2,6-piperidinedione,                                  hydrochloride 7   glutarimide       1,8-dibromooctane                  4-(4-trifluoromethylphenyl)-                                  1-[8-[3,6-dihydro-4-(4-trifluoro-                  1,2,3,6-tetrahydropyridine                                  metylphenyl)-1(2H)pyridinyl]octyl]-                                  .                                  2,6-piperidinedione,                                  hydrochloride 8   glutarimide       1,3-dibromo-2-                  4-(3-nitrophenyl)-1,2,3,6-                                  1-[3-[3,6-dihydro-4-(3-nitrophenyl)                                  -       methylpropane                  tetrahydropyridine                                  1(2H)pyridinyl]-2-methylpropyl]-2,6                                  -                                  piperidinedione, hydrochloride 9   glutarimide       1,2-dibromoethane                  4-(2-aminophenyl)-1,2,3,6-                                  1-[2-(3,6-dihydro-4-(2-aminophenyl)                                  -                  tetrahydropyridine                                  1(2H)pyridinyl]ethyl]-2,6-piper-                                  idinedione, hydrochloride10   glutarimide       1,3-dibromopropane                  4-(2-cyanophenyl)-1,2,3,6-                                  1-[3-[3,6-dihydro-4-(2-cyanophenyl)                                  -                  tetrahydropyridine                                  1(2H)pyridinyl]propyl]-2,6-piper-                                  idinedione, hydrochloride11   succinimide       1,2-dibromoethane                  4-phenyl-1,2,3,6-tetrahydro-                                  1-[2-[3,6-dihydro-4-phenyl-1-                  pyridine        (2H)pyridinyl]ethyl]-2,5-pyrrol-                                  idinedione, hydrochloride12   succinimide       1,8-dibromooctane                  4-(2-chlorophenyl)-1,2,3,6-                                  1-[8-[3,6-dihydro-4-(2-chloro-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]octyl]-                                  2,5-pyrrolidinedione, hydro-                                  chloride13   succinimide       1,3-dibromopropane                  4-(2-ethylphenyl)-1,2,3,6-                                  1-[3-[3,6-dihydro-4-(2-ethyl-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]propyl]-                                  2,5-pyrrolidinedione, hydro-                                  chloride14   succinimide       1,4-dibromobutane                  4-(2-ethoxyphenyl)-1,2,3,6-                                  1-[4-[3,6-dihydro-4-(2-ethoxy-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]butyl]-                                  2,5-pyrrolidinedione, hydro-                                  chloride15   succinimide       1,5-dibromopentane                  4-(2-ethylthiophenyl)-1,2,3-                                  1-[5-[3,6-dihydro-4-(2-ethyl-                  6-tetrahydropyridine                                  thiophenyl)-1(2H)pyridinyl]pentyl]-                                  2,5-pyrrolidinedione,                                  hydrochloride16   succinimide       1,6-dibromohexane                  4-(2-trifluoromethylphenyl)-                                  1-[6-[3,6-dihydro-4-(2-trifluoro-                                  methylphenyl)-1(2H)pyridinyl]hexyl]                                  -                                  2,5-pyrrolidinedione,                                  hydrochloride17   succinimide       1,7-dibromoheptane                  4-(4-nitrophenyl)-1,2,3,6-                                  1-[7-[3,6-dihydro-4-(4-nitrophenyl)                                  -                  tetrahydropyridine                                  1(2H)pyridinyl]heptyl]-2,5-pyrroli-                                  dinedione, hydrochloride18   succinimide       1,2-dibromoethane                  4-(4-aminophenyl)-1,2,3,6-                                  1-[2-[3,6-dihydro-4-(4-amino-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]ethyl]-                                  2,5-pyrrolidinedione, hydro-                                  chloride19   succinimide       1,5-dibromo-3-                  4-(4-cyanophenyl)-1,2,3,6-                                  1-[5-[3,6-dihydro-4-(4-cyano-       methylpentane                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]-3-                                  methylpentyl]-2,5-pyrrolidine-                                  dione, hydrochloride20   adipimide       1,2-dibromoethane                  4-phenyl-1,2,3,6-tetrahydro-                                  1-[2-[3,6-dihydro-4-phenyl-1-                  pyridine        (2H)pyridinyl]ethyl]-2,7-homo-                                  piperidinedione, hydrochloride21   adipimide       1,3-dibromopropane                  4-(4-fluorophenyl)-1,2,3,6-                                  1-[3-[3,6-dihydro-4-(4-fluoro-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]propyl]-                                  2,7-homopiperidinedione, hydro-                                  chloride22   adipimide       1,3-dibromopropane                  4-(3-t-butylphenyl)-1,2,3,6-                                  1-[3-[3,6-dihydro-4-(3-t-butyl-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]propyl]-                                  2,7-homopiperidinedione, hydro-                                  chloride23   adipimide       1,4-dibromobutane                  4-(3-ethoxyphenyl)-1,2,3,6-                                  1-[4-[3,6-dihydro-4-(3-ethoxy-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]butyl]-                                  2,7-homopiperidinedione, hydro-                                  chloride24   adipimide       1,5-dibromopentane                  4-(4-ethylthiophenyl)-1,2,3,6-                                  1-[5-[3,6-dihydro-4-(4-ethylthio-                  tetrahydropyridine                                  phenyl)-1(2H)pyridinyl]pentyl]-2,7-                                  homopiperidinedione, hydrocloride25   adipimide       1,6-dibromohexane                  4-(4-trifluoromethylphenyl)-                                  1-[6-[3,6-dihydro-4-(4-trifluoro-                  1,2,3,6-tetrahydropyridine                                  methylphenyl)-1(2H)pyridinyl]hexyl]                                  -                                  2,7-homopiperidinedione,                                  hydrochloride26   adipimide       1,7-dibromoheptane                  4-(3-nitrophenyl)-1,2,3,6-                                  1-[7-[3,6-dihydro-4-(3-nitrophenyl)                                  -                  tetrahydropyridine                                  1(2H)pyridinyl]heptyl]-2,7-homopipe                                  r-                                  idinedione, hydrochloride27   adipimide       1,8-dibromooctane                  4-(3-aminophenyl)-1,2,3,6-                                  1-[-[3,6-dihydro-4-(3-aminophenyl)-                  tetrahydropyridine                                  1(2H)pyridinyl]octyl]-2,7-homopiper                                  -                                  idinedione, hydrochloride28   adipimide       1,2-dibromoethane                  4-(3-cyanohenyl)-1,2,3,6-                                  1-[2-[3,6-dihydro-4-(3-cyanophenyl)                                  -                  tetrahydropyridine                                  1(2H)pyridinyl]ethyl]-2,7-homopiper                                  -                                  idinedione, hydrochloride29   glutarimide       1,2-dibromoethane                  4-(4-chlorophenyl)piperidine                                  1-[2-[4-(4-chlorophenyl)piperidinyl                                  ]-                                  ethyl]-2,6-piperidinedione,                                  hydro-                                  chloride30   glutarimide       1,3-dibromopropane                  4-(4-bromophenyl)piperidine                                  1-[3-[4-(4-bromophenyl)piperidinyl]                                  -                                  propyl]-2,6-piperidinedione,                                  hydro-                                  chloride31   glutarimide       1,5-dibromopentane                  4-(2-methylphenyl)piperidine                                  1-[5-[4-(2-methylphenyl)piperidinyl                                  ]-                                  pentyl]-2,6-piperidinedione,                                  hydro-                                  chloride32   glutarimide       1,6-dibromohexane                  4-(3-methoxyphenyl)piperidine                                  1-[6-[4-(3-methoxyphenyl)piper-                                  idinyl]hexyl]-2,6-piperidinedione,                                  hydrochloride33   glutarimide       1,7-dibromoheptane                  4-(4-methyltiophenyl)piper-                                  1-[7-[4-(4-methylthiophenyl)piper-                  idine           idinyl]heptyl]-2,6-piperidinedione,                                  hydrochloride34   glutarimide       1,8-dibromooctane                  4-(4-trifluoromethylphenyl)-                                  1-[8-[4-(4-trifluoromethylphenyl)-                  piperidine      piperidinyl]octyl]-2,6-piperidine-                                  dione, hydrochloride35   glutarimide       1,3-dibromo-2-                  4-(3-nitrophenyl)piperidine                                  1-[3-[4-(3-nitrophenyl)piper-       methylpropane              idinyl]-2-methylpropyl]-2,6-                                  piperidinedione, hydrochloride36   glutarimide       1,2-dibromoethane                  4-(2-aminophenyl)piperidine                                  1-[2-[4-(2-aminophenyl)piperidinyl]                                  -                                  ethyl]-2,6-piperidinedione,                                  hydro-                                  chloride37   glutarimide       1,3-dibromopropane                  4-(2-cyanophenyl)piperidine                                  1-[3-[4-(2-cyanophenyl)piperidinyl[                                  -                                  propyl]-2,6-piperidinedione,                                  hydro-                                  chloride38   succinimide       1,2-dibromoethane                  4-phenylpiperidine                                  1-[2-(4-phenylpiperidinyl)ethyl]-                                  2,5-pyrrolidinedione,                                  hydrochloride39   succinimide       1,8-dibromooctane                  4-(2-chlorophenyl)piperidine                                  1-[-[4-(2-chlorophenyl)piperidinyl]                                  -                                  octyl]-2,5-pyrrolidinedione,                                  hydro-                                  chloride40   succinimide       1,3-dibromopropane                  4-(2-ethylphenyl)piperidine                                  1-[3-[4-(2-ethylphenyl)pipridinyl]-                                  propyl]-2,5-pyrrolidinedione,                                  hydro-                                  choride41   succinimide       1,4-dibromobutane                  4-(2-ethoxyphenyl)piperidine                                  1-[4-[4-(2-ethoxyphenyl)piper-                                  idinyl]butyl]-2,5-pyrrolidinedione,                                  hydrochloride42   succinimide       1,5-dibromopentane                  4-(2-ethylthiophenyl)piper-                                  1-[5-[4-(2-ethylthiophenyl)piper-                  idine           idinyl]pentyl]-2,5-pyrrolidinedione                                  ,                                  hydrochloride43   succinimide       1,6-dibromohexane                  4-(2-trifluoromethylphenyl)-                                  1-[6-[4-(2-trifluoromethylphenyl)-                  piperidine      piperidinyl]hexyl]-2,5-pyrrolidine-                                  dione, hydrochloride44   succinimide       1,7-dibromoheptane                  4-(4-nitrophenyl)piperidine                                  1-[7-[4-(4-nitrophenyl)piperidinyl]                                  -                                  heptyl]-2,5-pyrrolidinedione,                                  hydro-                                  chloride45   succinimide       1,2-dibromoethane                  4-(4-aminophenyl)piperidine                                  1-[2-[4-(4-aminophenyl)piperidinyl]                                  -                                  ethyl]-2,5-pyrrolidinedione,                                  hydro-                                  chloride46   succinimide       1,5-dibromo-3-meth-                  4-(4-aminophenyl)piperidine                                  1-[5-[4-(4-aminophenyl)piperidinyl]                                  -3-       ylpentane                  methylpentyl]-2,5-pyrrolidinedione,                                  hydrochloride47   adipimide       1,2-dibromoethane                  4-phenylpiperidine                                  1-[2-(4-phenylpiperidinyl)ethyl]-2,                                  7-                                  homopiperidinedione,                                  hydrochloride48   adipimide       1,3-dibromopropane                  4-(3-fluorophenyl)piperidine                                  1-[3-[4-(3-fluorophenyl)piperidinyl                                  ]-                                  propyl]-2,7-homopiperidinedione,                                  hydro-                                  chloride49   adipimide       1,3-dibromopropane                  4-(3-t-butylphenyl)piperidine                                  1-[3-[4-(3-t-butylphenyl)piper-                                  idinyl]propyl]-2,7-homopiperidine-                                  dione, hydrochloride50   adipimide       1,4-dibromobutane                  4-(3-ethoxyphenyl)piperidine                                  1-[4-[4-(3-ethoxyphenyl)piperidinyl                                  ]-                                  butyl]-2,7-homopiperidinedine,                                  hydro-                                  chloride51   adipimide       1,5-dibromopentane                  4-(4-ethylthiophenyl)piper-                                  1-[5-[4-(4-ethylthiophenyl)piperidi                                  nyl]-                  idine           pentyl]-2,7-homopiperidinedione,                                  hydro-                                  chloride52   adipimide       1,6-dibromohexane                  4-(4-trifluoromethylphenyl)-                                  1-[6-[4-(4-trifluoromethylphenyl)pi                                  per-                                  idinyl]-2,7-homopiperidinedione,                                  hydro-                                  chloride53   adipimide       1,7-dibromoheptane                  4-(3-nitrophenyl)piperidine                                  1-[7-[4-(3-nitrophenyl)piperidinyl]                                  heptyl]-                                  2,7-homopiperidinedione,                                  hydrochloride54   adipimide       1,8-dibromooctane                  4-(3-aminophenyl)piperidine                                  1-[8-[4-(3-aminophenyl)piperidinyl]                                  octyl]-                                  2,7-homopiperidinedione,                                  hydrochloride55   adipimide       1,2-dibromoethane                  4-(3-cyanophenyl)piperidine                                  1-[2-[4-(3-cyanophenyl)piperidinyl]                                  ethyl]-                                  2,7-homopiperidinedione,                                  hydrochloride__________________________________________________________________________
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Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4472408 *Mar 3, 1982Sep 18, 1984SanofiSubstituted trifluoromethylphenyltetrahydropyridines having an anorectic activity
US4602024 *Jul 16, 1984Jul 22, 1986SanofiSubstituted trifluoromethylphenyltetrahydropyridines having a cyano substituent and an anorectic activity, a process for preparing same and pharmaceutical compositions
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US5962477 *Jun 15, 1998Oct 5, 1999Adolor CorporationScreening methods for cytokine inhibitors
US5994372 *Sep 12, 1996Nov 30, 1999Regents Of The University Of CaliforniaPeripherally active anti-hyperalgesic opiates
US6166039 *Nov 24, 1998Dec 26, 2000Regents Of The Univ. Of CaliforniaPeripherally active anti-hyperalgesic opiates
US6190691Jun 15, 1998Feb 20, 2001Adolor CorporationMethods for treating inflammatory conditions
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US6576650Oct 23, 2000Jun 10, 2003Regents Of The University Of CaliforniaPeripherally active anti-hyperalgesic opiates
U.S. Classification540/524, 546/208, 546/194, 546/278.7, 546/188, 540/526
International ClassificationC07D211/88
Cooperative ClassificationC07D211/88
European ClassificationC07D211/88